Post-Transplant CD34+ Selected Stem Cell “Boost” for Mixed Chimerism after Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation in Children and Young Adults with Primary Immune Deficiencies

Abstract

Mixed chimerism and eventual graft loss occurs in a proportion of children with primary immune deficiencies receiving alemtuzumab, fludarabine, and melphalan reduced-intensity conditioning (RIC) regimens before allogeneic hematopoietic stem cell transplantation (HSCT). We investigated the usefulness of a CD34 selected stem cell "boost" without conditioning to treat mixed chimerism in children and young adults who received predominantly an alemtuzumab, fludarabine, and melphalan RIC regimen for primary immune deficiencies and reported the outcomes. Patients with a primary immune deficiency disorder who were either enrolled on a prospective CD34 boost study for treatment of mixed chimerism from 2011 to 2014 (n = 9) or treated with a CD34 boost on a clinical basis from 2014 to 2016 (n = 3) were included in this analysis. Response to a CD34 boost was defined as a rise in donor chimerism by ≥15% with donor chimerism of at least 20%, stabilization was defined as a rise in chimerism by <15% with donor chimerism ≥ 20%, and no response was defined as any decline in donor chimerism or need for a second HSCT after a CD34 boost. Twelve patients received alemtuzumab, fludarabine, and melphalan. Median age was 4.5 years (range, .9 to 20.6), and median whole blood donor chimerism before the boost was 25% (range, 3% to 61%). Three patients (25%) met criteria for response, 1 patient (8%) was considered to have stabilization, and 8 patients (67%) had no response 12 months after the boost. None of the patients developed any complications from a CD34 boost, including no acute graft-versus-host disease (GVHD). All patients are alive with a median follow-up of 32 months (range, 8 to 79). We conclude that a CD34 selected stem cell boost can be considered for treatment of mixed chimerism after alemtuzumab, fludarabine, and melphalan RIC HSCT in children and young adults with primary immune deficiencies. Approximately one-third of patients can be expected to benefit from a CD34 selected stem cell boost and may avoid the need for a second HSCT. Lack of any GVHD or toxicity makes a stem cell boost an attractive option compared with donor lymphocyte infusions for treatment of mixed chimerism.

CD34+ selected peripheral blood Stem Cell Boost (SCB) for Poor Graft Function (PGF) or mixed chimerism in pediatric patients, after hematopoietic stem cell transplantation: Results of a retrospective multicenter study

“…In our series of patients, two out of three patients had undergone transplantation for cancer. Moreover, the low GVHD developed made stem cell boost an attractive option compared with donor lymphocyte infusions for treatment of mixed 19 Our series of patients also confirmed a higher survival probability for patients with only one deficient line (71%) compared to those with 2 deficient lines (44%), although not reaching statistical significance.…”

“…Moreover, Cuadrado et al were able to show, in a mixed pediatric and adult population, how the OS was significantly related to PGF response to CD34+ boost. They reported a 5‐year overall survival rate of 74.4% (95% CI 59‐89) in patients demonstrating complete recovery, 16.7% (95% CI 3‐46) in patients with partial recovery, and 22.2% (CI 95% 5‐47) in patients with no response 19 . Our series of patients also confirmed a higher survival probability for patients with only one deficient line (71%) compared to those with 2 deficient lines (44%), although not reaching statistical significance.…”

Haploidentical Transplantation in a DNA Ligase IV Deficiency Patient: A Case Report and Review of The Literature

“…Chandra reported twelve patients with immune deficiency received RIC regimen including alemtuzumab, fludarabine, and melphalan. Approximately one-third of patients can be expected to benefit from donor CD34+ selected stem cells infusion and may avoid the need for a second HSCT, and the infusion was well tolerated without any complications, including GvHD [24] . Besides donor CD34+ selected stem cells infusion, donor lymphocyte infusion(DLI) was also used to deal with mixed chimerism after transplantation in those patients.…”

G‐CSF administration prior to donor lymphocyte apheresis promotes anti‐leukaemic effects in allogeneic HCT patients

“…One of the most significant parameters for improved OS was the increased number of CD34 + stem and progenitor cells produced by G‐CSF administration prior to donor lymphocyte collection. It is an established procedure to administer purified CD34 + cells after allo‐HCT in case of mixed chimerism or poor graft function (Chandra et al , ; Mainardi et al , ). Moreover, CD34 + stem cell dose is one of the most important parameters to evaluate graft quality and predict haematopoietic recovery in autologous‐ and allo‐HCT settings (Weaver et al , ; Allan et al , ; Torlen et al , ; Rezvani et al , ).…”